PI(4,5)P 2 -dependent regulation of exocytosis by amisyn, the vertebrate-specific competitor of synaptobrevin 2
The functions of nervous and neuroendocrine systems rely on fast and tightly regulated release of neurotransmitters stored in secretory vesicles through SNARE-mediated exocytosis. Few proteins, including tomosyn (STXBP5) and amisyn (STXBP6), were proposed to negatively regulate exocytosis. Little is...
Saved in:
Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 24; pp. 13468 - 13479 |
---|---|
Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
16.06.2020
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | The functions of nervous and neuroendocrine systems rely on fast and tightly regulated release of neurotransmitters stored in secretory vesicles through SNARE-mediated exocytosis. Few proteins, including tomosyn (STXBP5) and amisyn (STXBP6), were proposed to negatively regulate exocytosis. Little is known about amisyn, a 24-kDa brain-enriched protein with a SNARE motif. We report here that full-length amisyn forms a stable SNARE complex with syntaxin-1 and SNAP-25 through its C-terminal SNARE motif and competes with synaptobrevin-2/VAMP2 for the SNARE-complex assembly. Furthermore, amisyn contains an N-terminal pleckstrin homology domain that mediates its transient association with the plasma membrane of neurosecretory cells by binding to phospholipid PI(4,5)P
However, unlike synaptrobrevin-2, the SNARE motif of amisyn is not sufficient to account for the role of amisyn in exocytosis: Both the pleckstrin homology domain and the SNARE motif are needed for its inhibitory function. Mechanistically, amisyn interferes with the priming of secretory vesicles and the sizes of releasable vesicle pools, but not vesicle fusion properties. Our biochemical and functional analyses of this vertebrate-specific protein unveil key aspects of negative regulation of exocytosis. |
---|---|
AbstractList | The functions of nervous and neuroendocrine systems rely on fast and tightly regulated release of neurotransmitters stored in secretory vesicles through SNARE-mediated exocytosis. Few proteins, including tomosyn (STXBP5) and amisyn (STXBP6), were proposed to negatively regulate exocytosis. Little is known about amisyn, a 24-kDa brain-enriched protein with a SNARE motif. We report here that full-length amisyn forms a stable SNARE complex with syntaxin-1 and SNAP-25 through its C-terminal SNARE motif and competes with synaptobrevin-2/VAMP2 for the SNARE-complex assembly. Furthermore, amisyn contains an N-terminal pleckstrin homology domain that mediates its transient association with the plasma membrane of neurosecretory cells by binding to phospholipid PI(4,5)P
However, unlike synaptrobrevin-2, the SNARE motif of amisyn is not sufficient to account for the role of amisyn in exocytosis: Both the pleckstrin homology domain and the SNARE motif are needed for its inhibitory function. Mechanistically, amisyn interferes with the priming of secretory vesicles and the sizes of releasable vesicle pools, but not vesicle fusion properties. Our biochemical and functional analyses of this vertebrate-specific protein unveil key aspects of negative regulation of exocytosis. Significance Exocytosis is of vital importance for life, as it allows cells to communicate with each other and with their environment. This dynamic process is highly regulated with a set of both positive and negative regulators. While promotors of exocytosis are well studied, negative regulators are poorly understood. We discovered that a small SNARE protein amisyn (STXBP6) acts as a vertebrate-specific competitor of synaptobrevin-2, a key player in exocytosis. Amisyn contains an N-terminal pleckstrin homology domain that mediates its transient association with the plasma membrane by binding to phospholipid PI(4,5)P 2 . Both the pleckstrin homology and SNARE domains are needed to inhibit exocytosis. Understanding the mechanisms by which amisyn regulates exocytosis will advance our comprehension of pathological processes in diabetes and autism. The functions of nervous and neuroendocrine systems rely on fast and tightly regulated release of neurotransmitters stored in secretory vesicles through SNARE-mediated exocytosis. Few proteins, including tomosyn (STXBP5) and amisyn (STXBP6), were proposed to negatively regulate exocytosis. Little is known about amisyn, a 24-kDa brain-enriched protein with a SNARE motif. We report here that full-length amisyn forms a stable SNARE complex with syntaxin-1 and SNAP-25 through its C-terminal SNARE motif and competes with synaptobrevin-2/VAMP2 for the SNARE-complex assembly. Furthermore, amisyn contains an N-terminal pleckstrin homology domain that mediates its transient association with the plasma membrane of neurosecretory cells by binding to phospholipid PI(4,5)P 2 . However, unlike synaptrobrevin-2, the SNARE motif of amisyn is not sufficient to account for the role of amisyn in exocytosis: Both the pleckstrin homology domain and the SNARE motif are needed for its inhibitory function. Mechanistically, amisyn interferes with the priming of secretory vesicles and the sizes of releasable vesicle pools, but not vesicle fusion properties. Our biochemical and functional analyses of this vertebrate-specific protein unveil key aspects of negative regulation of exocytosis. |
Author | Jakhanwal, Shrutee Meinecke, Michael Jahn, Reinhard Milosevic, Ira Kondratiuk, Ilona Pobbati, Ajaybabu V Sathyanarayanan, Udhayabhaskar Fasshauer, Dirk Jin, Jialin Krisko, Anita Ashery, Uri Kroppen, Benjamin |
Author_xml | – sequence: 1 givenname: Ilona orcidid: 0000-0002-7740-8923 surname: Kondratiuk fullname: Kondratiuk, Ilona organization: European Neuroscience Institute Göttingen, University Medical Center Göttingen and the Max-Planck Society, 37077 Göttingen, Germany – sequence: 2 givenname: Shrutee surname: Jakhanwal fullname: Jakhanwal, Shrutee organization: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany – sequence: 3 givenname: Jialin surname: Jin fullname: Jin, Jialin organization: European Neuroscience Institute Göttingen, University Medical Center Göttingen and the Max-Planck Society, 37077 Göttingen, Germany – sequence: 4 givenname: Udhayabhaskar surname: Sathyanarayanan fullname: Sathyanarayanan, Udhayabhaskar organization: European Neuroscience Institute Göttingen, University Medical Center Göttingen and the Max-Planck Society, 37077 Göttingen, Germany – sequence: 5 givenname: Benjamin surname: Kroppen fullname: Kroppen, Benjamin organization: Institute for Cellular Biochemistry, University Medical Center Göttingen, 37075 Göttingen, Germany – sequence: 6 givenname: Ajaybabu V surname: Pobbati fullname: Pobbati, Ajaybabu V organization: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany – sequence: 7 givenname: Anita surname: Krisko fullname: Krisko, Anita organization: Department of Experimental Neurodegeneration, University Medical Center Göttingen, 37073 Göttingen, Germany – sequence: 8 givenname: Uri surname: Ashery fullname: Ashery, Uri organization: School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Sagol School of Neuroscience, Tel Aviv University, 6997801 Tel Aviv, Israel – sequence: 9 givenname: Michael orcidid: 0000-0003-1414-6951 surname: Meinecke fullname: Meinecke, Michael organization: Institute for Cellular Biochemistry, University Medical Center Göttingen, 37075 Göttingen, Germany – sequence: 10 givenname: Reinhard orcidid: 0000-0003-1542-3498 surname: Jahn fullname: Jahn, Reinhard organization: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany – sequence: 11 givenname: Dirk orcidid: 0000-0002-1040-4282 surname: Fasshauer fullname: Fasshauer, Dirk organization: Département des Neurosciences Fondamentales, Université de Lausanne, 1015 Lausanne, Switzerland – sequence: 12 givenname: Ira orcidid: 0000-0001-6440-3763 surname: Milosevic fullname: Milosevic, Ira email: imilose@gwdg.de organization: European Neuroscience Institute Göttingen, University Medical Center Göttingen and the Max-Planck Society, 37077 Göttingen, Germany; imilose@gwdg.de |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32467162$$D View this record in MEDLINE/PubMed |
BookMark | eNpFkMlLAzEchYNU7KJnb5KjQqfNNttRikuhYEHvQ5ZfdKRNhiQtzn9vS11O7_K-B-8bo4HzDhC6pmRGScnnnZNxRmtSMc4oLc_QiJKaZoWoyQCNCGFlVgkmhmgc4ychpM4rcoGGnImipAUbIb9e3oppfrfGDGcGOnAGXMIB3ncbmVrvsLcYvrzuk49txKrHctvG3k1x-gC8h5BABZkgix3o1rYaa7_tILXJhyN7qMoueRVg3zrMLtG5lZsIVz85Qa-PD2-L52z18rRc3K8yzXieslJICZXmXFuuqeGKm8qqgoOULD9cNFaVxJhK5ZyRqlYFtZyVFVE5LYXgEzQ_rergYwxgmy60Wxn6hpLmKK45imv-xR2ImxPR7dQWzF__1xT_BhrtbFk |
CitedBy_id | crossref_primary_10_1126_sciadv_abf3873 crossref_primary_10_3390_genes12122020 crossref_primary_10_1515_nf_2020_0032 crossref_primary_10_3390_brainsci11040436 crossref_primary_10_3390_ijms242216436 crossref_primary_10_1016_j_celrep_2023_112036 crossref_primary_10_3389_fnmol_2022_1062878 crossref_primary_10_3390_ijms25021146 |
Cites_doi | 10.1074/jbc.274.22.15440 10.1016/S0896-6273(00)80472-9 10.1038/srep42573 10.1074/jbc.272.44.28036 10.1016/S0092-8674(00)81404-X 10.7554/eLife.38880 10.1038/ncomms14236 10.1038/ejhg.2008.71 10.1038/nprot.2015.053 10.1007/s00424-006-0143-9 10.1016/0092-8674(95)90239-2 10.1074/jbc.M204929200 10.7554/eLife.41711 10.1016/0092-8674(93)90376-2 10.1074/jbc.M408767200 10.1016/j.bbamem.2015.03.026 10.1083/jcb.123.6.1835 10.1016/S0014-5793(99)00028-9 10.1016/S0022-2836(05)80360-2 10.1038/642 10.1016/S0896-6273(00)00131-8 10.1083/jcb.201609046 10.1074/jbc.M305500200 10.1002/j.1460-2075.1989.tb03388.x 10.1016/S0962-8924(98)01285-9 10.2337/db15-1489 10.1083/jcb.109.6.3039 10.1093/molbev/msn151 10.1126/science.1129486 10.1038/nature14975 10.1007/978-1-59745-178-9_24 10.1074/jbc.M505858200 10.1006/jmbi.2000.4042 10.1083/jcb.113.2.245 10.2337/dbi16-0019 10.1523/JNEUROSCI.3761-04.2005 10.1146/annurev-cellbio-111315-125349 10.1016/j.mrfmmm.2010.02.007 10.1093/nar/gki524 10.1007/BF00713279 10.1038/26412 10.1073/pnas.85.12.4538 10.1038/356060a0 10.1093/hmg/ddq013 10.1038/nmeth782 10.1126/science.1321498 10.1007/978-1-4939-8719-1_11 10.1021/bi980542h |
ContentType | Journal Article |
DBID | NPM AAYXX CITATION |
DOI | 10.1073/pnas.1908232117 |
DatabaseName | PubMed CrossRef |
DatabaseTitle | PubMed CrossRef |
DatabaseTitleList | PubMed CrossRef |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Sciences (General) |
EISSN | 1091-6490 |
EndPage | 13479 |
ExternalDocumentID | 10_1073_pnas_1908232117 32467162 |
Genre | Journal Article |
GroupedDBID | --- -DZ -~X .55 0R~ 123 29P 2AX 2FS 2WC 4.4 53G 5RE 5VS 85S AACGO AAFWJ AANCE ABBHK ABOCM ABPLY ABPPZ ABTLG ABXSQ ABZEH ACGOD ACIWK ACNCT ACPRK ADACV AENEX AEUPB AEXZC AFFNX AFOSN AFRAH ALMA_UNASSIGNED_HOLDINGS AQVQM BKOMP CS3 D0L DCCCD DIK DOOOF DU5 E3Z EBS F5P FRP GX1 H13 HH5 HYE IPSME JAAYA JBMMH JENOY JHFFW JKQEH JLS JLXEF JPM JSG JST KQ8 L7B LU7 N9A NPM N~3 O9- OK1 PNE PQQKQ R.V RHF RHI RNA RNS RPM RXW SA0 SJN TAE TN5 UKR VQA W8F WH7 WOQ WOW X7M XSW Y6R YBH YKV YSK ZCA ~02 ~KM AAYXX CITATION |
ID | FETCH-LOGICAL-c235t-74aae8c33cf3c1d3b3d8fb63eaa25109dfb70dd8b532089b61f32780b517443 |
ISSN | 0027-8424 |
IngestDate | Fri Aug 23 01:31:42 EDT 2024 Sat Sep 28 08:26:55 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 24 |
Keywords | exocytosis inhibition autism spectrum disorders SNARE complex tomosyn PI(4,5)P2 |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c235t-74aae8c33cf3c1d3b3d8fb63eaa25109dfb70dd8b532089b61f32780b517443 |
ORCID | 0000-0003-1414-6951 0000-0003-1542-3498 0000-0002-1040-4282 0000-0002-7740-8923 0000-0001-6440-3763 |
OpenAccessLink | https://www.pnas.org/content/pnas/117/24/13468.full.pdf |
PMID | 32467162 |
PageCount | 12 |
ParticipantIDs | crossref_primary_10_1073_pnas_1908232117 pubmed_primary_32467162 |
PublicationCentury | 2000 |
PublicationDate | 2020-06-16 |
PublicationDateYYYYMMDD | 2020-06-16 |
PublicationDate_xml | – month: 06 year: 2020 text: 2020-06-16 day: 16 |
PublicationDecade | 2020 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | Proceedings of the National Academy of Sciences - PNAS |
PublicationTitleAlternate | Proc Natl Acad Sci U S A |
PublicationYear | 2020 |
References | e_1_3_3_50_2 e_1_3_3_16_2 e_1_3_3_18_2 e_1_3_3_39_2 e_1_3_3_12_2 e_1_3_3_37_2 e_1_3_3_14_2 e_1_3_3_35_2 e_1_3_3_33_2 e_1_3_3_10_2 e_1_3_3_31_2 e_1_3_3_40_2 Terrian D. M. (e_1_3_3_1_2) 1997; 73 e_1_3_3_5_2 e_1_3_3_7_2 e_1_3_3_9_2 e_1_3_3_27_2 e_1_3_3_29_2 e_1_3_3_23_2 e_1_3_3_48_2 e_1_3_3_25_2 e_1_3_3_46_2 e_1_3_3_44_2 e_1_3_3_3_2 e_1_3_3_21_2 e_1_3_3_42_2 e_1_3_3_17_2 e_1_3_3_19_2 e_1_3_3_38_2 e_1_3_3_13_2 e_1_3_3_36_2 e_1_3_3_15_2 e_1_3_3_34_2 e_1_3_3_32_2 e_1_3_3_11_2 e_1_3_3_30_2 e_1_3_3_6_2 e_1_3_3_8_2 e_1_3_3_28_2 e_1_3_3_49_2 e_1_3_3_24_2 e_1_3_3_47_2 e_1_3_3_26_2 e_1_3_3_45_2 e_1_3_3_2_2 e_1_3_3_20_2 e_1_3_3_43_2 e_1_3_3_4_2 e_1_3_3_22_2 e_1_3_3_41_2 |
References_xml | – ident: e_1_3_3_26_2 doi: 10.1074/jbc.274.22.15440 – ident: e_1_3_3_13_2 doi: 10.1016/S0896-6273(00)80472-9 – ident: e_1_3_3_21_2 doi: 10.1038/srep42573 – ident: e_1_3_3_23_2 doi: 10.1074/jbc.272.44.28036 – ident: e_1_3_3_27_2 doi: 10.1016/S0092-8674(00)81404-X – ident: e_1_3_3_11_2 doi: 10.7554/eLife.38880 – ident: e_1_3_3_41_2 doi: 10.1038/ncomms14236 – ident: e_1_3_3_18_2 doi: 10.1038/ejhg.2008.71 – ident: e_1_3_3_45_2 doi: 10.1038/nprot.2015.053 – ident: e_1_3_3_33_2 doi: 10.1007/s00424-006-0143-9 – ident: e_1_3_3_12_2 doi: 10.1016/0092-8674(95)90239-2 – ident: e_1_3_3_14_2 doi: 10.1074/jbc.M204929200 – ident: e_1_3_3_17_2 doi: 10.7554/eLife.41711 – ident: e_1_3_3_5_2 doi: 10.1016/0092-8674(93)90376-2 – ident: e_1_3_3_25_2 doi: 10.1074/jbc.M408767200 – ident: e_1_3_3_31_2 doi: 10.1016/j.bbamem.2015.03.026 – ident: e_1_3_3_48_2 doi: 10.1083/jcb.123.6.1835 – ident: e_1_3_3_42_2 doi: 10.1016/S0014-5793(99)00028-9 – ident: e_1_3_3_43_2 doi: 10.1016/S0022-2836(05)80360-2 – volume: 73 start-page: 198 year: 1997 ident: e_1_3_3_1_2 article-title: Phylogenetic analysis of membrane trafficking proteins: A family reunion and secondary structure predictions publication-title: Eur. J. Cell Biol. contributor: fullname: Terrian D. M. – ident: e_1_3_3_35_2 doi: 10.1038/642 – ident: e_1_3_3_34_2 doi: 10.1016/S0896-6273(00)00131-8 – ident: e_1_3_3_47_2 doi: 10.1083/jcb.201609046 – ident: e_1_3_3_24_2 doi: 10.1074/jbc.M305500200 – ident: e_1_3_3_9_2 doi: 10.1002/j.1460-2075.1989.tb03388.x – ident: e_1_3_3_2_2 doi: 10.1016/S0962-8924(98)01285-9 – ident: e_1_3_3_16_2 doi: 10.2337/db15-1489 – ident: e_1_3_3_7_2 doi: 10.1083/jcb.109.6.3039 – ident: e_1_3_3_22_2 doi: 10.1093/molbev/msn151 – ident: e_1_3_3_28_2 doi: 10.1126/science.1129486 – ident: e_1_3_3_10_2 doi: 10.1038/nature14975 – ident: e_1_3_3_36_2 doi: 10.1007/978-1-59745-178-9_24 – ident: e_1_3_3_49_2 – ident: e_1_3_3_15_2 doi: 10.1074/jbc.M505858200 – ident: e_1_3_3_44_2 doi: 10.1006/jmbi.2000.4042 – ident: e_1_3_3_40_2 doi: 10.1083/jcb.113.2.245 – ident: e_1_3_3_38_2 doi: 10.2337/dbi16-0019 – ident: e_1_3_3_29_2 doi: 10.1523/JNEUROSCI.3761-04.2005 – ident: e_1_3_3_39_2 doi: 10.1146/annurev-cellbio-111315-125349 – ident: e_1_3_3_20_2 doi: 10.1016/j.mrfmmm.2010.02.007 – ident: e_1_3_3_46_2 doi: 10.1093/nar/gki524 – ident: e_1_3_3_32_2 doi: 10.1007/BF00713279 – ident: e_1_3_3_3_2 doi: 10.1038/26412 – ident: e_1_3_3_8_2 doi: 10.1073/pnas.85.12.4538 – ident: e_1_3_3_37_2 doi: 10.1038/356060a0 – ident: e_1_3_3_19_2 doi: 10.1093/hmg/ddq013 – ident: e_1_3_3_50_2 doi: 10.1038/nmeth782 – ident: e_1_3_3_6_2 doi: 10.1126/science.1321498 – ident: e_1_3_3_30_2 doi: 10.1007/978-1-4939-8719-1_11 – ident: e_1_3_3_4_2 doi: 10.1021/bi980542h |
SSID | ssj0009580 |
Score | 2.4052022 |
Snippet | The functions of nervous and neuroendocrine systems rely on fast and tightly regulated release of neurotransmitters stored in secretory vesicles through... Significance Exocytosis is of vital importance for life, as it allows cells to communicate with each other and with their environment. This dynamic process is... |
SourceID | crossref pubmed |
SourceType | Aggregation Database Index Database |
StartPage | 13468 |
Title | PI(4,5)P 2 -dependent regulation of exocytosis by amisyn, the vertebrate-specific competitor of synaptobrevin 2 |
URI | https://www.ncbi.nlm.nih.gov/pubmed/32467162 |
Volume | 117 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3JbtswECXc9NJL0XRNN_DQgwNFrkVS2zHogthBDQFOgNwMkiLhIIUUyDJa92P7LR2SWuzABdJeBFugCZnzNDNc3jyEPlCd5xAViR-xlPpMaHilRCp9zaRQsQhCqQzf-dssOrtk06vwajD4vXVqaV2Lkfy1l1fyP1aFe2BXw5L9B8t2ncIN-Az2hStYGK73snE2gfyQwSiFMKHPPOL5raZt7VVOZL7JB9XPUm7q0lQfgXyTg3E31t2YtNMoMpvt41r5hndpzg7Zk-aGf1baTQRozG_hzTdHgguPbCe0WRcAV-1xg1m7vnjas1UaF7LyfC-b9drH52WRGwiurU-efC-LLkpM-c2SFz-sHoE3X1brWnUYnDYSYjDC1x2455DLbnjBK26utsFlvoQvYslXN7zaXt8gRgbHd_TLjm8AcZQ5pvVIOTcNWY5B13jHjzsSaAPYpr1zywFlTrynifGWP7s3gIDHM6rHBV-NAqsGT9pud0p13wmh3cFGu6Uf04XpYNF38AA9JHEamsWBz5PzraLQiaNINf-wLT0V0493nmAna9qZ_9g86OIJetxMYPCpQ-MhGqjiKTps7YuHTR3z42eozCZDdhIeZ5jgHpi4ByYuNe6BicUGO2CeYIAR3gNL3MPS_HYHlpg8R_OvXy4-nfmNvocvCQ1rP2acq0RSKjWVQU4FzRMtIqo4h6x7nOZaxOM8T4QRL0lSEQWakjgZC1NdndEX6KAoC_UKYaHHCRepEIHWjCck5VpJpiIJc5FQ6_QIDdvRW9y6Ii6Lv1jqCL10o9s1hBlHZMqsvb5_J2_Qox7Jb9FBXa3VO8hda_HeAuAPEXmbdg |
link.rule.ids | 315,786,790,27957,27958 |
linkProvider | Flying Publisher |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=PI%284%2C5%29P+2+-dependent+regulation+of+exocytosis+by+amisyn%2C+the+vertebrate-specific+competitor+of+synaptobrevin+2&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+-+PNAS&rft.au=Kondratiuk%2C+Ilona&rft.au=Jakhanwal%2C+Shrutee&rft.au=Jin%2C+Jialin&rft.au=Sathyanarayanan%2C+Udhayabhaskar&rft.date=2020-06-16&rft.issn=0027-8424&rft.eissn=1091-6490&rft.volume=117&rft.issue=24&rft.spage=13468&rft.epage=13479&rft_id=info:doi/10.1073%2Fpnas.1908232117&rft.externalDBID=n%2Fa&rft.externalDocID=10_1073_pnas_1908232117 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0027-8424&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0027-8424&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0027-8424&client=summon |